80
D. Enders, M.R.M. Hüttl, O. Niemeier
99:01 dr), and we were pleased that in all cases nearly complete enantiocontrol (97% to ≥98% ee) was reached.
This cascade reaction generates four stereogenic centers, and theoretically could give rise to 2
4 = 16 different stereoisomers. We note that
in fact this asymmetric cascade forms enantioselectively just two diastereomers (α-nitro epimers), which are easy to separate by flash chromatography. The reason for the high stereoselectivity is the first Michael
addition, which is known to proceed with high diastereo- and enantioselectivity (List et al. 2001; Enders and Seki 2002). Clearly this selectivity
is kept or enhanced in the second step via a sterically favorable interaction between the iminium species and the nitroalkane (Prieto et al.
2005). The relative and absolute configurations of the cyclohexene carbaldehydes 72 were determined by
1 H-NMR (NOE) experiments and
X-ray crystallography in several cases, which are in agreement with respective related organocatalytic conjugate additions.
In addition, we used this method to develop a one-pot procedure to
construct polyfunctionalized tricyclic carbon frameworks, which contain up to eight stereogenic centers, with high stereocontrol (Scheme 18)
(Enders et al. 2007b). Such functionalized decahydroacenaphthylene (n
= 0) and decahydrophenalene (n = 1) carbon cores are typical structural
features of diterpenoid natural products, such as the hainanolides and
amphilectanes (Piers and Romero 1993; Li et al. 2004). The assembly
of the condensed polycyclic structures 76 and 77 was accomplished by
using the organocatalyzed domino Michael/Michael/aldol condensation
sequence (Enders and Hüttl 2006) starting from the simple aldehyde 73,
which already bears a diene moiety, and the substrates 74 and 75, followed by an intramolecular Diels-Alder reaction (IMDA).
As shown in Scheme 18, the domino reaction was carried out without
any change in the reaction conditions. After consumption of the starting
materials, the mixture was diluted with dichloromethane and cooled to
–78°C, and an excess of dimethylaluminum chloride was added to ensure complete conversion of the intermediates. When the reaction was
complete, the title compounds 76 or 77 were successfully isolated after
separation of the minor isomers by flash chromatography. The one-pot
synthesis was applicable to a range of different substrates, and through
variation of the chain length of the residue R
1 , the ring size can be adjusted to five- or six-membered rings. We observed very good yields
D. Enders, M.R.M. Hüttl, O. Niemeier
99:01 dr), and we were pleased that in all cases nearly complete enantiocontrol (97% to ≥98% ee) was reached.
This cascade reaction generates four stereogenic centers, and theoretically could give rise to 2
4 = 16 different stereoisomers. We note that
in fact this asymmetric cascade forms enantioselectively just two diastereomers (α-nitro epimers), which are easy to separate by flash chromatography. The reason for the high stereoselectivity is the first Michael
addition, which is known to proceed with high diastereo- and enantioselectivity (List et al. 2001; Enders and Seki 2002). Clearly this selectivity
is kept or enhanced in the second step via a sterically favorable interaction between the iminium species and the nitroalkane (Prieto et al.
2005). The relative and absolute configurations of the cyclohexene carbaldehydes 72 were determined by
1 H-NMR (NOE) experiments and
X-ray crystallography in several cases, which are in agreement with respective related organocatalytic conjugate additions.
In addition, we used this method to develop a one-pot procedure to
construct polyfunctionalized tricyclic carbon frameworks, which contain up to eight stereogenic centers, with high stereocontrol (Scheme 18)
(Enders et al. 2007b). Such functionalized decahydroacenaphthylene (n
= 0) and decahydrophenalene (n = 1) carbon cores are typical structural
features of diterpenoid natural products, such as the hainanolides and
amphilectanes (Piers and Romero 1993; Li et al. 2004). The assembly
of the condensed polycyclic structures 76 and 77 was accomplished by
using the organocatalyzed domino Michael/Michael/aldol condensation
sequence (Enders and Hüttl 2006) starting from the simple aldehyde 73,
which already bears a diene moiety, and the substrates 74 and 75, followed by an intramolecular Diels-Alder reaction (IMDA).
As shown in Scheme 18, the domino reaction was carried out without
any change in the reaction conditions. After consumption of the starting
materials, the mixture was diluted with dichloromethane and cooled to
–78°C, and an excess of dimethylaluminum chloride was added to ensure complete conversion of the intermediates. When the reaction was
complete, the title compounds 76 or 77 were successfully isolated after
separation of the minor isomers by flash chromatography. The one-pot
synthesis was applicable to a range of different substrates, and through
variation of the chain length of the residue R
1 , the ring size can be adjusted to five- or six-membered rings. We observed very good yields